Initial Market Assessment High Throughput Method for Plasma Exosomal Lipid Analysis for Early Cancer Detection 2143 1

Commercial Opportunity Summary Title: High Throughput Method for Plasma Exosomal Lipid Analysis for Early Cancer Detection Key Advantages: May provide a more accurate detection of exosomes from whole peripheral blood May provide greater speed of detection with higher reproducibility and ease of use May provide a platform for new biomarker diagnostics Market Opportunities: A long standing goal in cancer biology has been to develop tests for early cancer detection through the use of noninvasive methods, most notably liquid biopsies. Exosomes are important biological carriers of information found in circulating blood, lymph, urine and saliva and are considered “representatives” of a cellular phenotype and genotype. The steady state level of circulating exosomes in adult human plasma has been found to be as much as three times higher in individuals with certain carcinomas, and a positive correlation has been established between the level of exosomes and tumor stage in many different cancers. These data suggest exosomes as a clinically applicable biomarker candidate to be included in the rapidly growing molecular oncology diagnostics market. However, current exosome analysis methods are incompatible with clinical laboratories as the methods are too slow, inconvenient, inaccurate and expensive for routine use. Technology Solution: Researchers at the University of Kentucky have developed a miniaturized microfluidic device that can purify exosomes from small volumes of whole peripheral blood. In contrast to currently available exosome purification methods requiring lengthy incubation periods and limited sample analysis, this device produces a 10-fold higher yield in a fraction of the time. Other advantages, depending on which existing commercially-available test it is compared to, may include superior sensitivity, specificity, convenience, economy of cost, space and technical time. Another major advantage of this test is that it also has the ability to perform FT-MS for quantitative lipid profiling, unlike most PDMS-based microfluidic devices.

Inventor Objectives Expected Grant; Use of Grant Proceeds/ Patent: Current prototype developments have been funded by inventors’ start up package Inventors’ have applied for multiple NIH and NCI grants (status pending) Prototype modifications, testing and refinement Commercialization Inventor Timeline: Grant runs out in May Finalize antibody library to be used with device Convert prototype from manual to automatic Inventor relationships Started project at University of Louisville; UofL holds a license Subcontract to University of Alabama Birmingham (UAB) New device originally apart of startup (provisional patent filed) Previous communications with BCAL; no future partnerships with them desired Inventor commercialization goals Start-up company Clinical screening tool (diagnostic companies; biotech; clinical laboratories) Research tool (academic laboratories) Inventors are seeking a patent to finalize the design, componentization and testing of efficacy and thereafter begin commercialization together with any strategic partners.

Technology High Throughput Method for Plasma Exosomal Lipid Analysis for Early Cancer Detection 4

Automated microfluidic devices for cancer diagnostics The Problem: Current exosomal purification methods are incompatible with clinical laboratories Classical exosome purification methods from whole blood samples require a lengthy process, large machinery (ultracentrifugation machine) and are limited to a small number of samples that can be purified in a working day. The technology process is not suitable for clinical laboratories There is a need for a next generation solution, enabling transition to a high throughput method for plasma exosomal lipid analysis which will outperform the current process in terms of performance, time and cost Automated microfluidic devices use affinity capture to purify exosomes from whole peripheral blood in a fraction of the time Automated microfluidic devices deliver 10-fold higher yield of exosomes and greater reproducibility Automated microfluidic devices are small and can be made disposable for the use in clinical settings as a biomarker diagnostic tool Differential Ultracentrifugation (UC) The Solution: Automated microfluidic devices for cancer diagnostics (automated) Microfluidic device 5

Technology Development Stage (e.g., licensed for further development; product design/development) Advanced Evaluation: (e.g., Beta prototype or working prototype in situ Evaluation: (e.g., human testing or Alpha prototype Proof-of-Concept / IP Protection: (e.g., Animal testing and/or patents filed) Discovery: Basic principles observed and reported Assessment Gather Technology development process / time Prototype has been developed and tested. Working towards automation Stage 1 Stage 2 Stage 3 Notes: Current prototype is manual (push-pull method). Still developing custom antibodies. . 6

Top Relevant Patent Owners Worldwide Company Name Total assets # of Issued Patents # of Applications Avg. of Remaining Life * Avg. of Priority Year * The Broad Institute, Inc. 36 - 2013 Reneuron Ltd 28 EXOSOME DIAGNOSTICS, INC. 37 2012 University of Louisville 24 10 14 12 2008 Caris Life Sciences, Inc. 20 9 11 United Therapeutics Corporation Samsung Electronics Co., Ltd. 8 Roche Holding Ltd. 7 2011 Harvard University Massachusetts Institute Of Technology Hitachi, Ltd. 2 The University Of Texas System 6 1 2013 (with one filed in 1998) Tengion, Inc., Pennsylvania 5 2010 Partners Healthcare System, Inc., Massachusetts 2009 7

Relevant Patent Landscape (using exosome microvesicle) N =368 1. Technology Landscape. Tools: Innography

Active Innovation Landscape Patent, revenue, and patent enforcement per company 1. Technology Landscape. Tools: Innography.

Market High Throughput Method for Plasma Exosomal Lipid Analysis for Early Cancer Detection 10

Market Applications Application 1 Application 2 Application 3 Liquid biopsy diagnostic tool Research and Development for biotechnology firms Basic science research tool Considerations Considerations Considerations Cancer liquid biopsy market is fastest growing sector; GRAIL (owned by Illumina) aggregated over $300M in funds for the month of January 2016 US is fastest growing market due to completion of human genome project; ethical privacy issues; lack of skilled technicians A wide range of environment applications and unexploited opportunities are likely to open new market avenues Source: Carbon Markets.pptx. 11

Preliminary Market Takeaways Market Application Market Size Market Growth Rate Current Consumer Demand Potential Partners Notes Global liquid biopsy market $1.6 billion (2015) 22.3% 5 year CAGR (cancer sector is 36.2%) Growing support of medical communities drives growth, specifically clinical evidence Global oncology molecular diagnostics market $1.26 billion (2014) 17.8% High demand for personalized treatments; Ethical, privacy and practical issues Biotechnology Reagents market $56.4 billion 9% R&D expenditure triggers growth; rising cost of products and huge R&D expenses impede growth Key: = High/Large/many = Moderate = Low/Small/few 12